Protection against intestinal infection

Team of researchers identifies molecular mechanism

A special protein, known as T-bet, regulates the ability of the lymphocytes in our innate immune system to take part in early immune reactions to bacterial infections in the intestines. A team of researchers led by BIOSS member Prof Dr Andreas Diefenbach, Dr Yakup Tanriver and Dr Christoph Klose from the Institute of Medical Microbiology and Hygiene at the Freiburg University Medical Centre recently published these findings in the professional journal Nature.

The internal and external surfaces of the human body are home to many different kinds of bacteria; they even outnumber human cells by far. Most of these bacteria can be found in the intestines, where they are responsible for the microflora and normally live in symbiosis with our bodies. The microflora provides us with essential nutrients and protects us against bacterial infections.

In our innate immune system, we have a group of lymphocytes that can be found in the area of the internal and external surfaces of our body. These are critical for maintaining a balance between the local microflora and the human immune system. These lymphocytes can also take part in the immune system’s early response to different pathogens. However, when these cells malfunction because of a genetic predisposition or environmental factors, this can lead to infection or inflammatory bowel disease.

“How some lymphocytes can change from being protective to inducing inflammation was still not clear and was therefore the focus of our project," said Diefenbach, who is a member of the Centre of Chronic Immunodeficiency (CCI) at the Freiburg University Medical Centre and of the BIOSS Centre for Biological Signalling Studies cluster of excellence. The work done in this project is closely related to the research concept at the CCI.

The scientists at the Freiburg University Medical Centre were able to identify a type of cell in the mucosa of the intestines that develops only after birth. This population of lymphocytes has primarily protective properties, but when influenced by the local microflora and other factors these cells can develop a new protein, T-bet, and thus a pro-inflammatory profile. This is necessary, however, to trigger the early immune response against bacterial infections in the intestines due to salmonella, a common pathogen that causes diarrhoea in humans.

Further results of the study indicate that these cells also “play an important role in inflammatory bowel disease,” the researchers from Freiburg pointed out. Identifying this mechanism means it is now possible to develop therapies for treating intestinal infection and inflammatory bowel disease.

Original publication:

A T-bet gradient controls the fate and function of CCR6-ROR?t+ innate lymphoid cells.
Klose CS, Kiss EA, Schwierzeck V, Ebert K, Hoyler T, d'Hargues Y, Göppert N, Croxford AL, Waisman A, Tanriver Y, Diefenbach A.
Nature. 2013 Feb 14;494(7436):261-5.

http://www.nature.com/nature/journal/v494/n7436/full/nature11813.html